A phase I study of oral uracil/ftorafur (UFT) plus leucovorin and bis- acetato-ammine-dichloro-cyclohexylamine-platinum IV (JM-216) each given over 14 days every 28 days

Mark D. DeMario, Mark J. Ratain, Nicholas J. Vogelzang, Sridhar Mani, Everett E. Vokes, Gini F. Fleming, Kimberly Melton, Sheryl Johnson, Steven Benner, David Lebwohl

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15 Scopus citations


Purpose: To determine the feasibility, maximal tolerated doses, and response rates for a combined regimen of the platinum and 5-fluorouracil oral analogues bis-acetato-ammine-dichloro-cyclohexyl-amine platinum(IV) (JM-216) and uracil/ftorafur (UFT) coadministered as a 14 consecutive-day every 28- day schedule. Methods: Of 20 patients enrolled in this investigation, 17 on the following dose escalation scheme were evaluable for toxicity and/or response: I UFT 300 mg/day, JM-216 5 mg/day (three patients), II UFT 300 mg/day, JM-216 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten patients). Results: All 17 evaluable patients were evaluable for toxicity. At dose level III, dose-limiting nausea and emesis were observed in one patient despite maximal antiemetic support. Importantly, neurotoxicity and nephrotoxicity were not observed at the JM-216 dose levels examined in this study. This observation is consistent with results seen with single agent JM-216. Conclusion: For JM-216 and UFT administered at 20 mg/day and 300 mg/day over 14 days, nausea and emesis were observed as the principal dose-limiting toxicities. These doses are considerably below the maximally tolerated doses of single agent JM-216 and UFT. Shorter administration schedules should be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.

Original languageEnglish (US)
Pages (from-to)385-388
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Issue number5
StatePublished - Mar 18 1999
Externally publishedYes



  • Advanced cancer
  • Hyperemesis
  • JM-216
  • Oral chemotherapy
  • UFT

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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